Biomedical subjects
Nobuyuki Shiba
Publications and source records attributed to Nobuyuki Shiba.
[Ventricular assist system].
Despite the recent remarkable advances in the medical treatment for severe end-stage heart failure, we still need a more powerful therapy to save patients presenting with cardiogenic shock or progressive cardiac deterioration. The implantation of ventricular assist system (VAS) is one of the available strategies in such patients and it has been used as a bridge to recovery or a bridge to transplantation. Because of the severe shortage of brain -dead donors, the role of VAS is now expanding into an alternative to transplantation, which is called a destination therapy. This review summarizes the current application and the future direction of VAS therapy for end -stage heart failure in Japan.
Accumulation of risk markers predicts the incidence of sudden death in patients with chronic heart failure.
BACKGROUND: Sudden death is common in chronic heart failure (CHF). Risk stratification is the first step for primary prevention. AIM: To evaluate the use of risk markers for estimating sudden death risk. METHODS AND RESULTS: We prospectively examined 680 stable patients with CHF. Risk markers were evaluated using the Cox's proportional hazard model in a stepwise manner. Ejection fraction <30%, left ventricular end-diastolic diameter >60 mm, brain natriuretic peptide >200 pg/ml, non-sustained ventricular tachycardia, and diabetes were significantly associated with increased risk of sudden death. When the number of risk markers were included as co-variables, only "number of risk markers >or=3'' entered the model (hazard ratio 8.95, 95% confidence interval 4.57-17.52), while the effects of individual markers did not enter the model. The annual mortality from sudden death was 11% in patients with 3 or more risk markers and 1.4% in patients with 2 or less. CONCLUSIONS: Rather than particular risk markers, the number of accumulated risk markers was a more powerful predictor for sudden death in patients with CHF. The number of risk markers could be useful for risk stratification of sudden death.
High serum erythropoietin level is associated with smaller infarct size in patients with acute myocardial infarction who undergo successful primary percutaneous coronary intervention.
OBJECTIVES: We investigated whether a higher serum erythropoietin (EPO) level in patients with acute myocardial infarction (MI) subjected to successful primary percutaneous coronary intervention (PCI) can predict a smaller infarct size determined by creatine kinase (CK) release. BACKGROUND: Erythropoietin has been shown to protect cardiomyocytes from ischemia-reperfusion injury in rodents. METHODS: We prospectively studied 101 patients with first MI who received successful primary PCI within 12 h from the onset of MI. Blood samples were collected to examine the serum EPO level after the primary PCI and within 24 h from the onset of MI. RESULTS: The peak CK level and cumulative CK release were significantly lower in the above-median EPO group than in the below-median EPO group. Thrombolysis In Myocardial Infarction (TIMI) grades and collateral grades before PCI, infarct-related coronary arteries, time to the successful reperfusion from the onset of MI, and serum creatinine levels were similar in the two EPO groups. A stepwise multiple regression analysis revealed that the absolute serum EPO level (mU/ml) as well as TIMI grades after PCI and preinfarction angina was an independent predictor for the cumulative CK release. CONCLUSIONS: These data suggest that a high endogenous EPO level can predict a smaller infarct size in patients with acute MI subjected to successful primary PCI. This might be attributed to the potentially protective effect of endogenous EPO against ischemia-reperfusion injury in humans.
Prognostic value of plasma brain natriuretic peptide combined with left ventricular dimensions in predicting sudden death of patients with chronic heart failure.
BACKGROUND: We evaluated a combined assessment of brain natriuretic peptide (BNP) with left ventricular dimensions as a prognostic marker for sudden death in patients with chronic heart failure (CHF). Ventricular dimensions and BNP are separately recognized as prognostic markers for sudden death in patients with CHF. METHODS AND RESULTS: CHF patients at Stage C and B were registered for a prospective study. From the database, we analyzed 417 patients with coronary arterial disease (CAD) or primary/secondary dilated cardiomyopathy (DCM). Main effects of BNP, left ventricular ejection fraction (EF), LV diastolic dimension (LVDD), and interaction of BNP with the EF and LVDD were tested with Cox's proportional hazard model. BNP in sudden death patients was significantly higher than that in event-free patients. Although multivariate analysis revealed that BNP by itself was not an independent risk factor for sudden death after adjustments, it was revealed that BNP entered the model via interaction with EF as a risk factor associating with sudden death. On the other hand, BNP was an independent risk factor associating with heart failure events (death and hospitalization), and BNP did not enter the model via an interaction with EF. CONCLUSION: BNP by itself was an independent risk factor for the heart failure events, but not for sudden death in CHF patients of the present study. However, BNP should be important in predicting sudden death when measured with EF.
Poor prognosis of Japanese patients with chronic heart failure following myocardial infarction--comparison with nonischemic cardiomyopathy.
BACKGROUND: Myocardial infarction (MI) is one of the major etiologies of chronic heart failure (CHF) in Japan. METHODS AND RESULTS: The prognoses of CHF patients after MI (n=283) were investigated by comparing them with those of CHF patients with nonischemic cardiomyopathy (NICM, n=310) from the CHF registry (CHART; n=1,154). The Kaplan-Meier (KM) analyses revealed that the 3-year all-cause mortality was significantly higher in the MI cohort compared with the NICM cohort (29.0% vs 12.4%, p<0.0005). Age/gender/treatment-adjusted KM analysis revealed significant differences only in the cohorts with preserved left ventricular ejection fraction (LVEF), defined as LVEF >45%, or in less symptomatic patients (New York Heart Association I or II). Multivariate Cox regression analysis showed that beta-blocker (BB) was associated with a significant reduction in mortality from cardiac causes, and either angiotensin-converting enzyme inhibitor or angiotensin receptor blocker (ACEI/ARB) was significantly related to the improvement of survival in the MI cohort (adjusted hazard ratio: 0.222 and 0.497, p<0.05), even though these medicines were used significantly less often in the MI cohort. CONCLUSIONS: Underlying MI has a significant impact on the survival of Japanese CHF patients, especially those with preserved LVEF or with fewer symptoms. The appropriate expansion of ACEI/ARB or BB therapy might be necessary to improve their survival.
Analysis of survivors more than 10 years after heart transplantation in the cyclosporine era: Stanford experience.
BACKGROUND: Truly long term survival post heart transplantation has become increasingly frequent over the past two decades. METHODS: We analyzed multiple clinical outcomes in the cohort of 140 patients in the Stanford database who underwent heart transplantation after the introduction of cyclosporine-based immunosuppression in 1980 and survived >10 years after transplantation. RESULTS: We found generally excellent functional status in these patients, but a high incidence of hypertension, renal dysfunction, and graft CAD as well as malignancy. CONCLUSION: With continued improvement in post-transplant survival rates, providing complex care for such long-term recipients as these will assume increasing clinical importance in the everyday practice of transplant medicine and these data highlight the problems to be anticipated.
Analysis of chronic heart failure registry in the Tohoku district: third year follow-up.
BACKGROUND: Because the real prognosis of Japanese patients with chronic heart failure (CHF) is still unknown, the aim of the present study was to clarify the prognosis and predictors for mortality of CHF patients using the Chronic Heart failure Analysis and Registry in Tohoku district (CHART). METHODS AND RESULTS: As of February 2003, 1,154 stable CHF patients with optimum standard therapy have been enrolled in the registry since February 2000 and of these, 175 died of some cause during the follow-up period (mean follow-up period, 1.9+/-0.9 years), giving 1- and 3-year all-cause mortality rates of 7.3% and 20.9%, respectively. Multivariate analysis showed that age at entry, diabetes, ventricular tachycardia, plasma concentration of brain natriuretic peptide (BNP), New York Heart Association (NYHA) functional class and rural residence were significantly associated with all-cause mortality (hazard ratio: 1.028, 1.940, 1.650, 1.001, 1.713, and 2.226). The 1-year all-cause mortality rates of CHF patients with a left ventricular ejection fraction <25%, left ventricular end-diastolic diameter > or =60 mm, BNP > or =500 pg/ml, NYHA > or = III, or with underlying coronary artery disease were 15.0%, 11.4%, 16.8%, 16.3%, and 10.8%, respectively. CONCLUSIONS: The prognosis of Japanese CHF patients with these predictors remains poor. A stratified approach is necessary to improve their survival and quality of life.
Post-operative conversion from cyclosporine to tacrolimus in heart transplantation: a single-center experience.
BACKGROUND: Tacrolimus is a potent calcineurin inhibitor that was introduced to heart transplantation in the early 1990s. The side-effect profile of tacrolimus is more favorable than that of cyclosporine and some reports have suggested an advantage of tacrolimus in the treatment of rejection. The present study was undertaken to determine whether a late conversion to tacrolimus affords these benefits to heart transplant recipients. METHODS: Charts from 109 patients who underwent conversion from cyclosporine to tacrolimus for recurrent rejection or adverse effects were retrospectively reviewed. RESULTS: During the year after conversion to tacrolimus, there was a significant decrease in treated rejection episodes. Conversion to tacrolimus rapidly resulted in an improved lipid profile. Two years after conversion blood pressure was significantly reduced. Apart from rejection, these benefits were found mainly among individuals converted to tacrolimus within 1 year of heart transplantation. CONCLUSIONS: Conversion from cyclosporine to tacrolimus is safe and results in a more favorable risk factor profile. However, most of the benefits are seen in individuals converted within 1 year of transplantation.
Longer-term risks associated with 10-year survival after heart transplantation in the cyclosporine era.
BACKGROUND: Long-term survival after heart transplantation is common in the cyclosporine era. However, there are few data documenting pre-transplant/peri-operative factors predictive of truly long-term survival (>10 years). The purpose of this study is to identify factors associated with 10-year survival after heart transplantation. METHODS: Our study population included 197 adults who survived >6 months and died <10 years after heart transplant (medium-term group) and 140 adults who survived >10 years after heart transplant (long-term group) between December 1980 and May 2001. A comparison was done between the two groups and we used multivariate analysis to identify which factors predicted 10-year survival. RESULTS: The long-term group had younger recipient and donor age, lower recipient body mass index at transplant, shorter waiting time and lower percentages of ischemic etiology/male recipient/non-white recipient. Kaplan-Meier plots of freedom from graft coronary artery disease and malignancy showed later onset patterns in the long-term group compared with the medium-term group. Multivariate analysis showed that white recipient, younger recipient and lower recipient body mass index at heart transplant were factors significantly associated with 10-year survival. CONCLUSIONS: Several pre-transplant/peri-operative factors were associated with survival beyond 10 years after heart transplantation. Stratified/tailored strategies based on these factors may be helpful to attain longer-term survival of recipients with higher risks.
[Centrosome isolation from cultured bladder cancer cells--p53 mutation and centrosome hyperamplification].
Centrosome hyperamplification occurs frequently in human cancers, and is the major contributing factor for chromosomal instability and aneuploidy. We examined centrosome hyperamplification in bladder cancer cell lines. Samples were incubated with antibodies to the centrosome protein gamma-tubulin. The cell line (RT-4), which has a wild-type p53 status, showed a well-regulated centrosome replication cycle. On the other hand, centrosome hyperamplification was observed in HT-1197 and HT-13r cancer cells by discontinuous sucrose gradient fractionation. We used sucrose gradient fractions enriched for centrosomes by the immunoblot analysis for the presence of gamma-tubulin, a major component of centrosomes. The fractions were then immunoblotted with anti-nucleophosmin/B23 (NPM) antibody. NPM is a primary target of CDK2-cyclin E in the initiation of centrosome duplication. The profile of NPM closely paralleled that of gamma-tubulin, suggesting the association of NPM with the centrosome. Identification of the mechanism underlying the replication of the centrosome should lead to the understanding of the mechanism of chromosomal instability in bladder cancer, and enable us to develop cancer therapeutics targeted to centrosome replication.